ol5b03625_si_001.pdf (2.23 MB)
C‑Terminal Modification of Fully Unprotected Peptide Hydrazides via in Situ Generation of Isocyanates
journal contribution
posted on 2016-03-04, 21:50 authored by Alexander
A. Vinogradov, Mark D. Simon, Bradley L. PenteluteA method
for chemo- and regioselective conjugation of nucleophiles
to fully unprotected peptides and proteins via in situ generation
of C-terminal isocyanates is reported. Oxidation of C-terminal peptide
hydrazides in aqueous media followed by Curtius rearrangement of acyl
azides reliably generates isocyanates, which react with a variety
of external nucleophiles, such as hydrazines, hydrazides, aromatic
thiols, and hydroxylamines. Multiple peptides and a 53 kDa protein
hydrazide were conjugated to different nucleophiles using this reaction.